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Biomedical subjects

M A Manuel

Publications and source records attributed to M A Manuel.

At least 19 recordsLinked to original sources
PubMed1998

Mass balance index: an index for adequacy of dialysis and nutrition.

Determining adequacy of dialysis has remained a problem for the nephrologist despite the results of the National Cooperative Dialysis Study published more than 20 years ago. Urea Kinetics Modelling (UKM) which requires computer data entry is time-consuming for the dialysis staff but is the only method that has been rigorously studied. Furthermore, it is unclear today what value of Kt/V represents ideal dialysis; the technique is subject to a number of errors associated with estimation of dialyser clearance (K) and volume of distribution of urea (V) but it is useful for calculating protein catabolic rate (PCR). Methods that use urea reduction ratios (URR) is widely used because it is simpler but not always accurate and suffer from an inability to calculate PCR. Direct dialysis quantification (DDQ) can overcome a number of these problems but it is too cumbersome for routine use. Simpler methods to determine dialysateside kinetics have the advantage of solving a number of these problems and also facilitate the calculation of PCR to determine the patient's nutritional state. In our study we have demonstrated that by taking two dialysate samples at the beginning and at the end of dialysis (2-DSM), it is possible to determine total urea removal (TUR) which is equivalent to DDQ. By taking blood samples after dialysis and before the next dialysis, it is possible to calculate the total urea generated (TUG). The ratio of TUR/TUG will provide an index of dialysis which places emphasis on removal of solute that has accumulated in the inter-dialytic interval thus re-establishing a state of equilibrium. We refer to this index as the Mass Balance Index (MBI). The MBI is also useful in helping to identify those patients whose PCR is inadequate since the mean MBI for patients with an nPCR <0.8 was 0.93 +/- 0.03 vs 1.08 +/- 0.02 in those with a PCR >0.8. In these two groups of patients the Kt/V was not significantly different, 1.49 +/- 0.07 vs 1.53 +/- 0.06, p -0.64. We suggest that the emphasis for adequacy of dialysis should shift away from Kt/V to maintaining a state of equilibrium by removing the solutes that accumulate between dialysis and by identifying those patients with an inadequate PCR.

Dialysis Solutions↗
PubMed1997

Quantitating dialysis using two dialysate samples: a simple, practical and accurate approach for evaluating urea kinetics.

Urea kinetics is now widely used to determine the adequacy of dialysis. Several simplified formulae are currently in use but only a few have been accepted into clinical practice because of their simplicity and ease of calculation. A recent analysis of these formulae showed that for the same set of blood urea values the calculated Kt/V can range from 1.0 to 1.5. We have developed a new dialysate-based method (2DSM) to estimate the urea kinetic parameters using dialysate and blood samples taken at the beginning and at the end of dialysis. The total urea removed (TUR) was calculated from the geometric mean of the two dialysate samples, dialysate flow rate and the duration of dialysis. The Watson formula was used to determine the volume of distribution of urea. A comparison of the 2DSM and the direct dialysate quantification (DDQ) method showed the following results (mean +/- sd, n = 52): for total urea removal (TUR) 697 +/- 32 vs 722 +/- 37 mmol (p = 0.6, r2 = 0.928, y = 101 + 0.83 x, mean difference 25 +/- 76 mmol, see Bland-Altman plot), dialysate urea concentration (Durea) 5.55 +/- 0.25 vs 5.75 +/- 0.29 mmol/l (p = 0.6, r2 = 0.928, y = 0.8 + 0.82 x, mean difference 0.2 +/- 0.6 mmol, see Bland-Altman plot), dialyser clearance (K) 232 +/- 4.4 vs 235 +/- 5.6 ml/min (p = 0.54), Kt/V 1.42 +/- 0.04 vs 1.51 +/- 0.04 (p = 0.21), volume of distribution of urea (Vd) 40.14 +/- 1.04 vs 38.74 +/- 1.2 L, (p = 0.38), and PCR 64.6 +/- 2.6 vs 68.1 +/- 3.1 g/day. We have developed a simple method of determining dialysate-based urea kinetics which requires two dialysate samples, one at the beginning and one at the end of dialysis and a blood sample at the midpoint of dialysis. TUR can be calculated using the dialysate flow rate and the dialysis duration and once this is known all the other kinetic parameters can be calculated.

Blood Specimen Collection↗
PubMed1989

Bioavailability of iron in oral ferrous sulfate preparations in healthy volunteers.

The bioavailability of iron in five ferrous sulfate preparations was studied in 10 healthy male volunteers. The preparations were an oral solution, two types of film-coated tablets and two types of enteric-coated tablets. Blood samples were drawn hourly from 8 am to 6 pm on the day before each study day to assess baseline serum iron concentrations and on the study day. Spectrophotometry was used to measure the serum iron concentrations. The area under the curve (AUC), the maximum concentration and the time to achieve the maximum concentration were compared by analysis of variance. The enteric-coated preparations resulted in AUCs less than 30% of the AUC for the oral solution. The two film-coated products produced AUCs essentially equivalent to that of the oral solution. We conclude that the bioavailability of iron in the enteric-coated preparations was low, relative to that of the film-coated products and the oral solution, and that these products should not be considered interchangeable.

Administration, Oral↗
PubMed1989

Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis (CAPD).

Ten adult patients on continuous ambulatory peritoneal dialysis (CAPD) received one dose of trimethoprim-320 mg (TMP) and sulfamethoxazole 1600 mg (SMX) orally (p.o.), intravenously (i.v.), and intraperitoneally (i.p.) on three separate occasions to characterize the pharmacokinetics of both drugs. Concentrations of both TMP and SMX were measured in serum and dialysate by HPLC to 48 h. Half-life, total body clearance (TBC), and peritoneal clearance (PCl) were determined. The mean half-life of TMP was 28 h, while for SMX it was 12.5 h. Relative to the i.v. dose, the bioavailability following oral administration for TMP was 98% and 87% for SMX. Intraperitoneal bioavailability was 73% for TMP and 65% for SMX after a 4-h dwell. After 24 h, regardless of the route of administration, less than 3% of TMP and less than 6% of SMX appeared in dialysate. We conclude that peritoneal losses contribute insignificantly to TMP/SMX elimination during CAPD.

Administration, Oral↗
PubMed1985

Bone mineral content in idiopathic calcium nephrolithiasis.

The calcium content of the central one third of the skeleton was measured using neutron activation analysis in 109 patients with idiopathic calcium nephrolithiasis. The bone mineral content (calcium bone index or CaBI, corrected for body size) was significantly decreased by 5.2% in 20- to 60-year-old patients with calcium nephrolithiasis (p less than 0.01). Under age 50 the decrease was more marked in 64 males (7.1%; p less than 0.02) than in 21 females (4.1%; p = NS). There was a significant negative correlation of CaBI with fasting urine calcium/creatinine ratio (r = 0.39; p less than 0.01), but no correlation with age or indices of parathyroid function. The decrease in bone mineral content did not appear to be progressive. The decrease in CaBI indicates negative calcium balance, either in the past or at present, in patients with calcium nephrolithiasis and does not favour increased intestinal absorption as a primary cause. The lack of correlation of CaBI with parameters of parathyroid function does not support a primary renal loss of calcium. The results suggest that increased bone turnover may be an important component of disordered calcium metabolism in patients with calcium nephrolithiasis.

Adult↗
PubMed1979

Nephrotoxicity and ototoxicity following irrigation of wounds with neomycin.

Renal failure and ototoxicity developed in two patients following wound irrigation with neomycin. In both patients the renal failure was reversible, but the deafness was progressive despite withdrawal of the neomycin. In one patient the serum neomycin concentration was still markedly elevated (42 microgram/ml) 2 days after use of the drug was discontinued. The authors suggest that irrigation of large open wounds with neomycin is dangerous since toxic blood concentrations may ensue. The benefits conferred by neomycin irrigation should be weighed against the possible danger of permanently impaired hearing.

Administration, Topical↗
PubMed1977

Effects of ethacrynic acid and furosemide on phosphorylation reactions of kidney mitochondria. Inhibition of the adenine nucleotide translocase.

Previous reports that ethacrynic acid and furosemide diminish mitochondrial P : O ratios and reduce (Na+ + K+)-ATPase activity suggested that these diuretics may inhibit mitochondrial phosphorylation reactions. This possibility was initially studied by determining the effects of ethacrynic acid and furosemide on [32P]ATP exchange activity of rat kidney mitochondria. Concentrations of both drugs at 10(-4) M or greater, significantly inhibited [32P]ATP exchange. To investigate the mechanism of this inhibition, the effects of ethacrynic acid and furosemide on the ATPase activity of intract mitochondria and sonicated submitochondrial particles were determined. Both diuretics inhibited ATPase activity of intact mitochondria at 10(-4) M. In contrast, ATPase of submitochondrial particles was significantly less susceptible to inhibition by the diuretics. These results suggested that ethacrynic acid anf furosemide inhibit adenine nucleotide transport across the mitochondrial membrane. This was directly tested by determining the effects of the diretics on the mitochondrial adenine nucleotide translocase. At 5-10(-4) M, both ethacrynic acid and furosemide significantly inhibited adenine nucleotide transport. These findings suggest that ethacrynic acid and furosemide may diminish renal tubular solute reabsorption by direct inhibition of adenine nucleotide transport across the mitochondrial inner membrane.

Adenosine Triphosphatases↗
PubMed1976

Effects of ethacrynic acid and furosemide on isolated rat kidney mitochondria: inhibition of electron transport in the region of phosphorylation site II.

Previous reports that ethacrynic acid and furosemide inhibit the respiration of isolated mitochondria suggested a direct action of these diuretics on oxidative metabolism. To explore this possibility further, the effects of ethacrynic acid and furosemide on the oxygen consumption of mitochondria isolated from the cortex and outer medulla of rat kidneys were investigated. Both diuretics inhibited state 3 and uncoupled respiration supported by glutamate-malate (which enters the electron transport chain prior to site I) and succinate (which enters prior to site II); respiration supported by tetramethyl phenylene diamine-ascorbate (which enters prior to site III) was relatively unaffected. Biochemical bypass of site II significantly alleviated the respiratory inhibition by both agents. Confirmation of these findings was provided by measurement of the electron transport carriers by dual wavelength spectroscopy, which showed that both diuretics caused a reduction of flavoproteins and an oxidation of the cytochromes. It is concluded that ethacrynic acid and furosemide inhibit oxidative phosphorylation in vitro by inhibiting electron transport through phosphorylation site II.

Animals↗
PubMed1975

Diuretics, urate excretion and sodium reabsorption: effect of acetazolamide and urinary alkalinization.

The uricosuric properties of acetazolamide were investigated in order to elucidate the relationship between changes in proximal tubular sodium reabsorption and urate excretion in man. Acetazolamide produced a modest uricosuric response which was not suppressible by pyrazinamide. Alkalinization of the urine with sodium bicarbonate elicited an even smaller increment in the urate clearance. If urinary alkalinization does play a role in the uricosuric response to acetazolamide, it probably decreases urate reabsorption within the distal nephron. The present studies, when taken together with previous work, suggest that alterations in proximal tubular sodium and water reabsorption probably do not play an important role in the normal control of urate excretion or in the pathogenesis of hyperuricemic states. Diuretic-induced hyperuricemia occurring during extracellular fluid volume depletion probably results from either diminished tubular secretion of urate, accelerated postsecretory urate reabsorption, or both.

Acetazolamide↗
PubMed1972

Role of venous needle hub in extracorporeal pressure changes during haemodialysis.

Certain types of stainless steel needles with metal hubs, and also a fistula set with projecting internal edges, were used at the venous end of the haemodialysis circuit and found to be associated with undesirable rises in extracorporeal pressure in 56 to 64% of dialyses. These increases in pressure are likely to be the result of platelet thrombus formation at the hub of the needle brought about by turbulent flow. The use of a plastic cannula and a stainless steel needle with a plastic hub, both of which have smooth internal surfaces, resulted in increases in pressure in only 4 to 12% of dialyses.

Aluminum↗